Our proposed research deals with environmental light damage to the retina of normal mice and rats and of those undergoing various forms of inherited retinal degeneration. We will study the damaging effects of fluorescent lighting at illuminance levels often found in office and industrial work environments. Our research objectives are three-fold. First, we shall clarify the sequence of cytopathologic steps in light damage and explore the possible role of the retinal pigment epithelium and the interphotoreceptor matrix in the degenerative process. To do this we will define the subcellular changes by quantitative electron microscopy. In addition, we will carry out studies using histochemistry, immunocytochemistry, and autoradiography of protein metabolism and transport or diffusion of various sugars. Second, we will study two determinants of the severity of light damage: eye pigmentation and genetic factors. To assess the protective role of eye pigmentation, we will use quantitative morphlogical methods and coisogenic and congenic strains of animals. To characterize the recently described genetic factors that regulate the susceptibility of the retina to light damage, we will use classical genetic crosses and recombinant inbred strains of mice to determine a) whether resistance to light damage is imparted by a single-gene or polygenic factor, b) the genetic mode of inheritance, and c) the chromosomal localization of the gene(s). In addition, we will probe the cellular and molecular mechanisms of resistance to light damage by the use of experimental mouse chimeras and collaborative biochemical studies. Third, we will examine the potentially damaging effects of light on the rate and character of the inherited retinal degenerations in the nervous and Purkinje cell degeneration mutant mice and in the RCS rat with inherited retinal dystrophy.